Functional antibodies as immunological endpoints to evaluate protective immunity against Shigella.

The development, clinical advancement and licensure of vaccines, and monitoring of vaccine effectiveness could be expedited and simplified by the ability to measure immunological endpoints that can predict a favorable clinical outcome. Antigen-specific and functional antibodies have been described in the context of naturally acquired immunity and vaccination against Shigella, and their presence in serum has been associated with reduced risk of disease in human subjects. The relevance of these antibodies as correlates of protective immunity, their mechanistic contribution to protection (e.g. target antigens, interference with pathogenesis, and participation in microbial clearance), and factors that influence their magnitude and makeup (e.g. host age, health condition, and environment) are important considerations that need to be explored. In addition to facilitating vaccine evaluation, immunological correlates of protection could be useful for identifying groups at risk and advancing immune therapies. Herein we discuss the precedent and value of functional antibodies as immunological endpoints to predict vaccine efficacy and the relevance of functional antibody activity to evaluate protective immunity against shigellosis.

What Is the Evidence to Support a Correlate of Protection for Measles? A Systematic Review.

BACKGROUND: Many studies assume that the serologic correlate of protection from measles disease is 120 mIU/mL. We systematically reviewed the literature to examine the evidence supporting this correlate of protection. METHODS: We searched peer-reviewed and gray literature for articles reporting a measles correlate of protection. We excluded studies focusing on special populations, infants aged <9 months, and those using animal models or nonstandard vaccines or administration routes. We extracted and synthesized data from full-text articles that met inclusion criteria. RESULTS: We screened 14 778 articles and included 5 studies in our review. The studies reported either preexposure antibody concentrations of individuals along with a description of symptoms postexposure, or the proportion of measles cases that had preexposure antibody concentrations above a threshold of immunity specified by the authors. Some studies also described secondary antibody responses upon exposure. The variation in laboratory methods between studies made comparisons difficult. Some of the studies that assumed 120 mIU/mL as a correlate of protection identified symptomatic individuals with preexposure titers exceeding this threshold. CONCLUSIONS: Our findings underscore the scant data upon which the commonly used 120 mIU/mL measles threshold of protection is based, suggesting that further work is required to characterize the measles immunity threshold.

Assessment of population immunity to measles in Ontario, Canada: a Canadian Immunization Research Network (CIRN) study.

Canada eliminated measles in 1998. We conducted a sero-epidemiology study to estimate population immunity to measles in the province of Ontario, Canada and to identify groups at higher risk of outbreaks. We used a previously developed modified enzyme immunoassay to test 1,199 residual sera from patients aged 1-39 years. We re-tested negative and equivocal sera using a plaque reduction neutralization assay. We interpreted our results in the context of Ontario's immunization program and vaccine coverage data. Of 1,199 sera, 1035 (86.3%, 95% confidence interval (CI) 84.4, 88.2) were above the measles threshold for protection, 70 (5.8%, 95% CI 4.5, 7.2) were equivocal and 94 (7.8%, 95% CI 6.3, 9.4) were negative. The proportion of positive sera was highest for those 1-5 years, with 180/199 (90.5%, 95% CI 86.4, 94.5) positive sera, and lowest for those age 12-19 years, at 158/199 (79.4%, 95% CI 73.8, 85.0). Adjusted for age, females were more likely than males to have antibody titers above the threshold of protection (odds ratio = 1.60, 95% CI 1.14, 2.24). Most of the study cohort were eligible for two measles vaccine doses, and vaccine uptake in Ontario is >90% for school-aged cohorts. We observed a higher than expected proportion of sera with antibody levels below the threshold of protection, suggesting that immunity in some Ontario age-groups may be waning, despite high vaccine coverage. Alternatively, the traditional measles correlates of protection may not be an appropriate measure of population protection in measles-eliminated settings.